The majority of herbal anticancer drugs are insoluble in water or become unstable during their transport to tumor tissues, hence they require a special drug delivery system. The main target of this study was to evaluate the therapeutic efficacy of silibinin (SLB)-loaded folic acid (FA)-conjugated Pluronic F127 (SLB-F127-FA) nanomicelles as an active-targeted drug delivery platform for liver cancer treatment. To prepare SLB-F127-FA nanomicelles, folic acid was first conjugated to hydrophilic chains of Pluronic F127 copolymer by the Steglich esterification technique. Then, silibinin was encapsulated in the self-assembled hydrophobic core of FA- conjugated F127 to render SLB-F127-FA nanomicelles. The prepared nano micelles had an almost spherical shape with an average particle size of 17.7 nm. The average hydrodynamic size of non-targeted (SLB-F127) and targeted (SLB-F127-FA) nanomicelles, measured by dynamic light scattering analysis (DLS), was 19.6 and 29.2 nm, respectively. Also, the drug loading content as well as entrapment efficiency of SLB-F127-FA nanomicelles were obtained to be 2.36% and 79.43%, respectively. The in vitro release patterns of SLB from nanomicelles showed a slow and sustained release behavior in comparison to free SLB. Moreover, it was observed that the kinetic release of silibinin from the SLB-F127-FA nanomicelles at 37 ◦ C conforms well to Korsmeyer-Peppas kinetic model (R 2 = 0.99, n = 0.22), suggesting a dominate release mechanism of the Fickian diffusion type. Moreover, in vitro cytotoxic study indicated that the viability of human liver cancer cells (HepG2) exposed to SLB-PF127-FA nanomicelles was significantly lower than that of treated with non-targeted nanomicelles (SLB- F127) or free SLB. Our results suggest that SLB-F127-FA nanomicelles can be considered as a promising targeted drug delivery platform for liver cancer therapy and/or delivering other hydrophobic drugs to different types of cancers with folate-receptor overexpression.
